There are presently a number of methods and techniques for the treatment of cancer and other diseases, among which may be included radiation therapy, chemotherapy, immunotherapy, and surgery. The common characteristic of all of these techniques as well as any other presently known techniques is that they are extracellular in scope; that is, the cancer or diseased cell is attacked and attempted to be killed through application of a killing force or medium outside of the cell. The only known exceptions are U.S. Pat. Nos. 4,106,488, 4,622,952, and 4,622,953, and this invention is an extension of the technologies described therein.
The extracellular approach however is less effective than the intracellular approach because of the difficulties of penetrating the outer membrane of the cancer or diseased cell that is composed of two protein layers with a lipid layer in between. Of even greater significance is that in order to overcome the protection afforded the cell by the cell membrane in any extracellular technique, the attack on the cancer or diseased cells must be of such intensity that considerable damage is caused to the normal cells resulting in severe side effects upon the subject. These side effects have been found to limit considerably the effectiveness and usefulness of these extracellular treatments.
A safe and effective cancer and disease treatment has been the goal of investigators for a substantial period of time. Such a technique to be successful in the destruction of the cancer or diseased cells must be selective in its effect upon the cancer or diseased cells and produce no irreversible damage to the normal cells. In sum, cancer and/or disease treatment must selectively differentiate cancer or diseased cells from normal cells and must selectively weaken or kill the cancer or diseased cells without affecting the normal cells.
It has been known that there are certain physical differences that exist between cancer and other diseased cells and normal cells. One primary physical difference is the temperature differential characteristics between the cancer and other diseased cells and the normal cells. Cancer cells and other diseased cells, because of their higher rates of metabolism, have higher resting temperatures than those of normal cells. In the living cell, the normal temperature of the cancer and other diseased cells is known to be 37.5.degree. Centigrade, while that of the normal cell is 37.degree. Centigrade. Another physical characteristic that differentiates the cancer and other diseased cells from the normal cells is that cancer and other diseased cells die at lower temperatures than do normal cells. The temperature at which a normal cell will be killed and thereby irreversibly will be unable to perform normal cell functions is a temperature of 46.5.degree. Centigrade, on the average. The cancer and other diseased cells, in contrast, are killed at the lower temperature of 45.5.degree. Centigrade. Thus, the temperature elevation increment necessary to cause death in the cancer or diseased cell is determined to be at least approximately 8.0.degree. Centigrade, while the normal cell can withstand a temperature increase of at least 9.5.degree. Centigrade.
It is known, therefore, that with a given precisely controlled increment of heat, the cancer or diseased cells can be selectively destroyed without injuring the normal cells. On the basis of this known differential in temperature characteristics, a number of extracellular attempts have been made to treat cancer and other diseases by heating the cancer or diseased cells in the body. This concept of treatment is referred to as hyperthermia. To achieve these higher temperatures in the cancer and diseased cells, researchers have attempted a number of methods including inducing high fevers, utilizing hot baths, diathermy, applying hot wax, and even the implantation of various heating devices in the area of the cancer or diseased cells.
Presently, none of the various known approaches to treat cancer and other diseases has been truly effective, and all have the common characteristic of approaching the problem by treating the cancer or diseased cells extracellularly. The only known exceptions are the techniques disclosed in the previously mentioned 4,106,488, 4,622,952 and 4,622,953 patents. The outer membrane of the cancer or diseased cell being composed of lipids and proteins is a poor thermal conductor, thereby making it difficult for heat which is applied by external means to penetrate into the interior of the cell where the intracellular temperature must be raised to effect the death of the cell. If, through the extracellular approaches of the prior hyperthermia techniques, the temperatures were raised sufficiently to effect an adequate intracellular temperature to kill the cancer or diseased cells, many of the normal cells adjacent the application of heat would be destroyed as well.
It has been known that the nuclei of cancer and other diseased cells and the nuclei of normal cells possess some differences. The alterations which occur in a cell to produce malignancy or disease either take place in, or are transmitted to, the nucleus. This is evident by the fact that the cells produced by the tumor and other diseased cells multiplication possess the same characteristics as the original tumor or diseased cells.
A large amount of work has been done "in vitro" concerning the magnetic resonant frequencies of cancer and other diseased cells as compared to those of normal tissues. Differences have been attributed to differences in the amount of water present in the cancer or diseased cells and the way in which the water molecules are ordered. A key to this process lies in the nuclear differences, including energy changes characteristic of structural and conformational changes in the deoxyribonucleic acid and the histones of the nucleus, including their relationship, resulting in differential resonant frequencies for the cancer or other diseased cells from the normal cells.
A further key to this process is the additional changes in intracellular biophysical characteristics which occur in this process. Included in these changes is the intracellular production of interleukins and other activators, such as interferons and prostaglandins. The production of interleukins, interleukin-like substances such as interleukin-1 (IL-1) and IL-2, and other activators can be triggered by alterations or changes in the cell's environment.
Unfortunately even if the interleukins or activators are synthesized and subsequently injected intravascularly into a subject, their effectiveness is limited due to the loss of time and specificity between injection into the subject and the time when the synthesized or isolated interleukins reach the cellular level where their effectiveness is required. Interleukins are most effective when stimulated intracellularly and their peak effectiveness and potential are utilized on the specific sites in the subject.
Additionally, this invention is secondarily directed to techniques for modulating the interaction of IL-2 and the cell to be activated and for modulating the interaction of NK cells and target cells. Prior art modulation techniques usually require that interleukin or some chemical substances be physically introduced into the subject. These substances however are often destroyed or altered, due to the body's metabolism activity, prior to reaching the cells to be changed. Therefore, these prior approaches are limited in their ability to modulate the interaction of interleukins and the cells to be activated.
This invention further relates to processes for treating atherosclerotic lesions. Present treatments involve surgery, balloon angioplasty or lasers. Surgery is of course an invasive procedure and recurrence often occurs in the grafted vessels. Balloon angioplasty involves the use of cardiac catheterization to place a guide wire and then a balloon in the lesion to dilate the lesion. Unfortunately, this is also invasive and requires cardiac catheterization with a significant recurrence rate and the danger of requiring immediate emergency surgery. The use of lasers to burn the lesions has been tried along with utilizing certain wavelengths of light in combination with porphyrins taken up by the plaque. The porphyrins which are taken up by the plaque respond to a certain wavelength. However, in order to get the light to the coronary artery, the laser must be introduced via catheterization which also is an invasive procedure.